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Birth Defects Res A Clin Mol Teratol. 2014 Apr;100(4):314-8. doi: 10.1002/bdra.23239. Epub 2014 Apr 7.

Further evidence for FGF16 truncating mutations as the cause of X-linked recessive fusion of metacarpals 4 / 5.

Author information

1
Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland; NZOZ Center for Medical Genetics GENESIS, Poznan, Poland.

Abstract

BACKGROUND:

Metacarpal 4-5 fusion (MF4; MIM#309630) is a rare congenital malformation of the hand characterized by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a genetic syndrome. Recently, we have identified FGF16 nonsense mutations as the underlying cause of isolated X-linked recessive MF4.

METHODS:

In this report, we provide a detailed clinical description of a sporadic male patient showing MF4 in whom we performed Sanger sequencing of the entire coding sequence of FGF16.

RESULTS:

In addition to MF4 symptoms, the patient presented with generalized joint laxity and hypermobility. FGF16 sequencing detected a novel truncating mutation (c.474_477del; p.E158DfsX25) in exon 3 of the gene. A heterozygous mutation was found in a clinically and radiologically unaffected mother of the proband.

CONCLUSION:

Our finding confirms that truncating mutations of FGF16 are causative for X-linked recessive metacarpal 4-5 fusion. Importantly, the mutation detected in this study was located in last exon of the gene (exon 3), like the only two FGF16 disease-causing variants identified to date. Thus, all FGF16 mutations known to give rise to this rare skeletal hand malformation are C-terminal and most probably do not result in a nonsense mediated decay. Additionally, our proband showed mild symptoms of a connective tissue disorder, as some other patients previously reported to have X-linked MF4. Therefore, we suggest that impaired FGF16 function may also be responsible for connective tissue symptoms in MF4 patients.

KEYWORDS:

FGF16; MF4; X-linked inheritance; connective tissue; metacarpal 4-5 fusion; metacarpal synostosis; truncating mutation

PMID:
24706454
DOI:
10.1002/bdra.23239
[Indexed for MEDLINE]
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